OBJECTIVE To study the improvement effects and mechanism of proanthocyanidins （PACs） on steroid-induced osteonecrosis of the femoral head （SONFH） in rabbits based on the receptor-interacting protein kinase 1 （RIPK1）/RIPK3/mixed lineage kinase domain-like protein （MLKL） signaling pathway. METHODS SONFH model in rabbits was induced by injecting Escherichia coli endotoxin+methylprednisolone. The successfully modeled rabbits were randomly divided into Model group （normal saline）， low-dose PACs group （PACs-L group， 11 mg/kg）， high-dose PACs group （PACs-H group， 22 mg/kg）， high-dose PACs+ RIPK1 activator （rRIPK1） group （PACs-H+rRIPK1 group， 22 mg/kg PACs+4 μg/kg rRIPK1）， along with a control group （normal saline）， with 6 rabbits in each group. Each administration group was given relevant medicine once a day intragastrically/via injection， for 4 consecutive weeks. After the last administration， the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in rabbit serum were measured. The changes in the microstructure of rabbit femurs， including bone mineral density （BMD）， trabecular thickness （Tb.Th）， trabecular number （Tb.N）， and trabecular separation （Tb. Sp） were examined. The histopathological features of rabbit femoral tissues were observed， and the apoptotic status of cells within the rabbit femoral tissues was detected. The mRNA expressions of vascular endothelial growth factor （VEGF） and bone morphogenetic protein 2 （BMP2） in rabbit femoral tissues were determined. The expressions of RIPK1/RIPK3/MLKL signaling pathway-related proteins in femoral tissues were detected. RESULTS Compared with the Control group， serum contents of TNF-α and IL-6， Tb.Sp， empty bone cavity rate， cell apoptosis rate， phosphorylation levels of RIPK1， RIPK3 and MLKL in femoral tissue were significantly increased in the Model group （P＜0.05）. BMD， Tb.Th， Tb.N， as well as the mRNA expression of VEGF and BMP2， along with protein expression of caspase-8， in the femoral tissues were all decreased （P＜0.05）. The bone cells in the femoral tissue were unevenly distributed， and the trabeculae were arranged sparsely. Compared with the Model group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in all dosage groups of PACs showed significant improvements. Compared with the PACs-H group， the aforementioned quantitative indicators （P＜0.05） and pathological changes in the PACs-H+rRIPK1 group showed significant reversal. CONCLUSIONS PACs can ameliorate SONFH in rabbits， and its mechanism of action may be related to the inhibition of the activation of the RIPK1/RIPK3/MLKL signaling pathway， suppression of apoptosis in femoral tissue cells， and promotion of angiogenesis.

OBJECTIVE To evaluate the economics of serplulimab combined with chemotherapy regimens for the first-line treatment of extensive-stage small cell lung cancer （ES-SCLC） from the perspective of health system in China. METHODS A partitioned survival model was constructed based on the ASTRUM-005 clinical trial and related literature data， with a model simulation time frame of 10 years and a 3-week cycle， and both cost and utility values were discounted using a 5% discount rate. The quality-adjusted life year （QALY） was used as a model output indicator and the incremental cost-effectiveness ratio （ICER） was calculated to evaluate the economics of serplulimab combined with chemotherapy regimens （serplulimab group） versus chemotherapy alone regimens （chemotherapy alone group） for the first-line treatment of ES-SCLC. One-way sensitivity analysis and probabilistic sensitivity analysis were used to verify the robustness of the results of the base-case analysis and to conduct a scenario analysis for the serplulimab patient assistance program. RESULTS The results of the base-case analysis showed that compared with chemotherapy alone group， ICER of serplulimab group was 758 690.27 yuan/QALY， which was higher than 3 times China’s per capita gross domestic product （GDP） in 2022 as the willingness-to-pay （WTP） threshold. The results of the scenario analysis showed that compared with chemotherapy alone group， the ICER of serplulimab group was 172 275.74 yuan/QALY， which was below above WTP threshold. The one-way sensitivity analysis showed that the progress-free survival utility value， serplulimab price and so on had a significant impact on the model results. The results of the probabilistic sensitivity analysis showed that the probability of the serplulimab group being economic was 0 when the serplulimab patient assistance program was not considered， but 100% when the patient assistance program was considered. CONCLUSIONS At a WTP threshold of 3 times China’s per capita GDP in 2022， the serplulimab group is no cost-effectiveness compared to the chemotherapy alone group； however， this result is reversed when the patient assistance program is taken into account.

Objective:To observe any effects of contralateral repeated transcranial magnetic stimulation (rTMS) of the swallowing motor cortex on the swallowing and brainstem auditory evoked potentials (BAEPs) of stroke survivors with dysphagia.Methods:A total of 83 stroke survivors with dysphagia were randomly divided into an ipsilesional stimulation group ( n=22), a contralesional stimulation group ( n=21), a bilateral stimulation group ( n=20), and a control group ( n=20). In addition to their conventional dysphagia training, those in the three stimulation groups received 3Hz rTMS while the control group was given fake stimulation. The treatment was administered daily for 20 minutes, 6 days a week, for 5 consecutive weeks. Before and after the treatment, swallowing function was assessed videofluoroscopically and using the Dysphagia Outcome and Severity Scale (DOSS). The oral and pharyngeal stages of swallowing were evaluated using the videofluoroscopic dysphagia scale (VDS). Brain stem conduction was assessed using BAEPs. Results:After treatment the average DOSS scores of all 4 groups were significantly better than before the treatment. The average DOSS scores of the contralesional and bilateral sti-mulation groups were then significantly better than those of the other two groups. The sub-item and total VDS scores of all 4 groups had decreased significantly, but the average score of the bilateral stimulation group was significantly lower than the control group′s average. Ipsilesional stimulation significantly improved the VDS sub-item scores for the triggering of pharyngeal swallowing, laryngeal elevation, and pharyngeal transit time compared with the control group. In the contralesional stimulation group the average total score and the VDS sub-item scores for apraxia, premature bolus loss, oral transit times, the triggering of pharyngeal swallowing, vallecular residue, laryngeal elevation, coating on the pharyngeal wall, and pharyngeal transit time were significantly lower than those of the control group, on average. After the treatment the latencies of BAEP waves I, III and V and the I-III, III-V and I-V interpeak intervals had decreased significantly in all four groups, but the average latencies and intervals of the bilateral and contralesional groups were significantly shorter than those of the control group. The latencies and intervals of the bilateral stimulation group were then significantly shorter than those in the ipsilesional stimulation group on average. The average latency of wave V in the bilateral stimulation group (6.53±0.73ms) was significantly shorter than that in the contralesional stimulation group after the treatment.Conclusion:Bilateral rTMS over the swallowing motor cortex combined with conventional dysphagia training can significantly improve the swallowing of dysphagic stroke survivors.

OBJECTIVE To systematically evaluate the economical efficiency of marketed a naplastic lymphoma kinase （ALK）-tyrosine kinase inhibitors （TKI）for the treatment of ALK-positive non-small cell lung cancer （NSCLC）in China ，and to provide a reference for the selection of China ’s medical insurance list and drug pricing. METHODS Computer searches of databases such as CNKI ，Wanfang database ，VIP，PubMed，Embase and the Cochrane Library were conducted to collect pharmacoeconomic evaluation studies of four marketed ALK-TKI （crizotinib，seretinib，aletinib and ensatinib ）in the treatment of ALK-positive NSCLC in China during the inception to July 2021. The qualities of the included literature were evaluated using CHEERS checklist ，and analyzed systematically in terms of both methodological and economic outcomes. RESULTS A total of 6 literatures were included ，with a compliance rate of 71％ to 83％ for the CHEERS list criteria ，and the overall quality of the literature was high. In terms of methodological analysis ，the pharmacoeconomic evaluation methods included in the study were mainly model-based （Markov or partitioned survival models ） and real-world data-based cost-utility analysis. Most research perspectives were health insurance payer and health system perspectives ；all cost types were direct medical costs. In terms of economical efficiency analysis ，compared with chemotherapy plan ，2 studies confirmed that ALK-TKI （crizotinib，seretinib）were not economic ，1 study confirmed ALK-TKI （crizotinib） showed economical efficiency. Seretinib showed relatively higher economical efficiency when compared to other ALK-TKIs. High drug prices were the main factor why ALK-TKI was not economically viable for treating ALK-positive NSCLC. CONCLUSIONS The second-generation ALK-TKI （seretinib， 163.com alectinib） have better economical efficiency than the first-generation ALK-TKI （crizotinib）. The economical efficiency of seretinib is the best among the second-generation · ALK-TKI. The economical efficiency of chemotherapy regimen is better than that of the second-generation ALK-TKI （seretinib）. Economic comparison between chemotherapy and first-generation ALK-TKI （crizotinib）remains controversial.

OBJECTIVE To evaluate the cost-utility of pembrolizumab combined with chemotherapy versus chemotherapy alone in the first-line treatment of advanced or metastatic esophageal carcinoma. METHODS Cost-utility analysis of pembrolizumab combined with chemotherapy versus chemotherapy alone for advanced or metastatic esophageal carcinoma was conducted by using a three-state partitioned survival model from the perspective of health system in China. The model use d a lifetime simulation time frame with 3 weeks as a cycle. The survival data were extrapolated using KEYNOTE- 590 data；cost data were obtained from the median of 2022 public winning bid on Yaozhi network ，among which the price of pembrolizumab was obtained after discounting by a patient assistance program ；utility data were obtained from the literatures ，and a 5％ discount rate was used for both cost and utility. One-way sensitivity analysis and probabilistic sensitivity analysis were also conducted to examine model robustness. RESULTS Analysis of the base case results showed that compared to chemotherapy alone ，the incremental cost-effectiveness ratio （ICER）of pembrolizumab combined with chemotherapy regimens were 950 528.42 yuan/QALY，107 845.39 yuan/QALY and 315 754.56 yuan/QALY for esophageal squamous cell carcinoma （ESCC），programmed deathligand- 1 combined positive score （PD-L1 CPS）≥10 and intention-to-treat population （ITT），respectively. The results of sensitivity analysis verified the robustness of the basic analysis results. CONCLUSIONS Under our healthcare system ，using a threshold of willingness-to-pay of 1-3 times our GDP per capita in 2021，pembrolizumab combined with chemotherapy regimen isn ’t cost-utility compared with chemotherapy alone in the ESCC and ITT subgroups of patients ，while it is cost-utility in the PD-L 1 CPS≥10 subgroup of patients.

OBJECTIVE To evaluate the cost-effectiveness of denosumab and zoledronic acid in the treatment of postmenopausal osteoporosis ，and to provide reference for relevant decision-making. METHODS From the perspective of Chinese health system ，Excel 2003 software was used to establish Markov model ，and cost-utility analysis was used to evaluate the cost-effectiveness of denosumab or zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis. Pharmacotherapy effects were obtained from the network Meta-analysis ，and cost and health-utility value data were obtained from the published literature or network ，etc. The model cycle was 1 year，and the simulation time limit was the patient ’s lifetime. One-way sensitivity analysis and probabilistic sensitivity analysis were used to evaluate the impact of model parameter changes on the robustness of the results ；and the cost-effectiveness of changing the medication cycle of zoledronic acid were explored through scenario analysis. RESULTS Denosumab regimen was more effective than zoledronic acid regimen （12.77 QALYs vs. 11.98 QALYs），and its cost was also higher than zoledronic acid regimen （51 224.56 yuan vs. 49 221.67 yuan）， and the incremental cost-effectiveness ratio was 2 544.14 yuan/QALY. One-way sensitivity analysis showed that the cost of Zoledronic acid injection and that of Denosumab injection had great impact on the results. The results of probabilistic sensitivity analysis showed that when using 3 times of per capita gross domestic product （GDP）in China in 2021 as the threshold of willingness to pay ，the probability of Denosumab regimen being cost-effective was 85.4％. The results of the scenario analysis showed that the Denosumab regimen was still more cost-effective when the dosing cycle of zoledronic acid was changed. CONCLUSIONS Under the threshold of 1-3 times of Chinese per capita GDP in 2021，denosumab combined with calcium carbonate D 3 is more cost-effective than zoledronic acid combined with calcium carbonate D 3 in the treatment of postmenopausal osteoporosis.

OBJECTIVE To evaluate the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia using a rapid health technology assessment （HTA） method， and provide an evidence-based basis for clinical decision-making. METHODS PubMed， Embase， Cochrane Library， CNKI， Wanfang database and foreign HTA official websites were systematically searched， and the search time frame of the databases was from the establishment of the database to May 25th 2022. After data extraction and quality evaluation of the literature according to the inclusion and exclusion criteria， a descriptive analysis of the effectiveness， safety and economy of iron isomaltoside in the treatment of iron deficiency anemia was performed. RESULTS & CONCLUSIONS A total of 1 HTA report， 3 systematic reviews/meta-analysis and 5 economic studies were included. In terms of effectiveness， compared with ferric carboxymaltose， the hemoglobin level of patients using iron isomaltoside increased more， but there was no significant difference in the proportion of responding patients； compared with iron sucrose， it had non- inferiority in increasing and maintaining hemoglobin level， and there was no difference in the quality of life. In terms of safety， the incidence of adverse events of ferric carboxymaltose， iron sucrose and iron isomaltoside were 12.0%， 15.3% and 17.0%， respectively. Iron isomaltoside had a lower incidence of hypophosphatemia， compared with ferric carboxymaltose. There was no statistical difference in the incidence of hypophosphatemia among iron isomaltoside， iron sucrose， iron-dextrin and nanocrystalline iron oxide. The conclusion of the incidence of treatment-emergent adverse event， the incidence of serious adverse events and the withdrawal rate of patients due to adverse events was not clear. In terms of economy， the economy of iron isomaltoside is better than that of iron sucrose， and the economy of iron isomaltoside versus that of ferric carboxymaltose had not been finalized.

OBJECTIVE To evaluate the cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer from the perspective of the Chinese health care system. METHODS A Markov model was developed by using updated four-year survival data from the PACIFIC trial in May 2021 and relevant literature. The cost-effectiveness of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer was evaluated by using quality-adjusted life years （QALYs）as health output index with 20-year simulation time frame and a 2-week cycling period. The costs and health output were discounted using discount rate of 5％；one-way sensitivity analysis and probabilistic sensitivity analysis were used to examine the robustness of the model simulation results. RESULTS The results of the base analysis showed that compared with placebo group ，durvalumab resulted in 0.73 QALYs at an incremental cost of 1 076 062.86 yuan and an incremental cost-utility ratio （ICER）of 1 467 546.54 yuan/QALY，which was much higher than 3-fold per capita gross domestic products （GDP）in 2020（217 713 yuan）as willingness-to-pay （WTP）threshold. The results of one-way sensitivity analysis showed that the price of durvalumab and discount rate had a great impact on ICER. Probabilistic sensitivity analysis showed no cost-effective advantage for durvalumab when the WTP threshold was three times of GDP per capita in 2020 （217 713 yuan）. CONCLUSIONS From the perspective of Chinese health care system ，there is no cost-effective advantage to the use of durvalumab for consolidation therapy after chemoradiotherapy for unresectable stage Ⅲ non-small cell lung cancer when the WTP threshold was three times of GDP per capita in 2020.

With improvements in information technology and expansion in education reforms, more innovative teaching reform programs have also been launched. Information technology has increased interest in the use of the flipped classroom innovative teaching model. In order to explore new ideas for the improvement of teaching, this paper focuses on the flipped classroom teaching approach with the integration of information technology. Micro-teaching is an important innovative flipped classroom teaching approach with a number of advantages as it is short, concise, and interesting, which therefore helps improve students' self-learning ability. Designing and preparing micro-teaching would become a prerequisite skill for college teachers. Based on the analysis of the entries in the "National Universities Micro-teaching Competition of Life Science", this paper explores the application of micro-teaching in life sciences teaching from the perspective of curriculum introduction, mode of presentation, teaching design, and other aspects of teaching. This information could serve as a guide to frontline college teachers to help them understand and master the skills of designing micro-teaching, so as to generate interest and improve learning efficiency among college students.
Biological Science Disciplines ; Curriculum ; Humans ; Learning ; Students ; Universities

BACKGROUND: Osteonecrosis of the femoral head (ONFH) following internal fixation of femoral neck fractures is difficult to be cured in clinic.OBJECTIVE: To analyze the literatures concerning ONFH in patients with femoral neck fractures treated with screw internal fixation in recent 15 years, and to summarize the research progress in views of epidemiology, etiology, diagnosis,treatment and rehabilitation.METHODS: Databases of CNKI, WanFang, CqVip, PubMed, Medline, Web of Science were searched with the keywords of femoral neck fracture, osteonecrosis of femoral head, osteonecrosis, internal fixation, internal fixation with screw in English and Chinese, respectively. Afterwards, the reviews and case reports were excluded. RESULTS AND CONCLUSION: (1) A total of 54 eligible articles addressing the ONFH following internal fixation for femoral neck fractures were included, and the incidence of ONFH varied from 8.1% to 37.2%, which was found at an average of 17 months after injury. (2) ONFH was found to be related to age, preoperative fracture displacement, preoperative traction,reduction condition, time from injury to operation, elderly patients companied with other diseases, older patients undergoing removal of the screws, closed or open internal fixation, restored time postoperatively, high body mass index, hyperlipidemia, season, and depression. (3) Early prevention and remedial surgery were used to treat ONFH. (4) The patients without weight-bearing activities at 3-6 months postoperatively could be beneficial for functional recovery. (5) These results suggest that choosing appropriate surgical programs and rehabilitation plan can reduce the incidence of ONFH and achieve good treatment outcomes, such as reasonable preoperative planning, standardized operation skills, correct diagnosis and treatment, proper postoperative rehabilitation and good doctor-patient cooperation.